CN117643588A - Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs - Google Patents
Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs Download PDFInfo
- Publication number
- CN117643588A CN117643588A CN202311506331.8A CN202311506331A CN117643588A CN 117643588 A CN117643588 A CN 117643588A CN 202311506331 A CN202311506331 A CN 202311506331A CN 117643588 A CN117643588 A CN 117643588A
- Authority
- CN
- China
- Prior art keywords
- rheumatoid arthritis
- nitrofurantoin
- application
- drugs
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 54
- NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 title claims abstract description 42
- 239000003814 drug Substances 0.000 title claims abstract description 40
- 229960000564 nitrofurantoin Drugs 0.000 title claims abstract description 37
- 229940079593 drug Drugs 0.000 title abstract description 24
- 230000003356 anti-rheumatic effect Effects 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 210000002437 synoviocyte Anatomy 0.000 claims abstract description 8
- 206010065687 Bone loss Diseases 0.000 claims abstract description 7
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 abstract description 8
- 102000004127 Cytokines Human genes 0.000 abstract description 5
- 108090000695 Cytokines Proteins 0.000 abstract description 5
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 229940124350 antibacterial drug Drugs 0.000 abstract description 5
- 230000035755 proliferation Effects 0.000 abstract description 5
- 238000012360 testing method Methods 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000010186 staining Methods 0.000 description 5
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010603 microCT Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 230000007480 spreading Effects 0.000 description 3
- 238000003892 spreading Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- -1 I L-6 Proteins 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- QVQLCTNNEUAWMS-UHFFFAOYSA-N barium oxide Chemical group [Ba]=O QVQLCTNNEUAWMS-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000004018 waxing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs, and belongs to the field of pharmaceutical chemistry. Rheumatoid arthritis is typically characterized by proliferation of synovial lining cells, while nitrofurantoin significantly reduces proliferation of synovial lining cells. In addition, nitrofurantoin can also remarkably inhibit osteoporosis and bone loss caused by rheumatoid arthritis, remarkably reduce the expression of inflammatory factors (IL-1β, I L-6, IL-17, IL-23), and promote the expression of anti-inflammatory cytokines (I L-10). The invention applies the nitrofurantoin which is originally used as an antibacterial drug to the treatment of the rheumatoid arthritis, enriches the drug types of the rheumatoid arthritis and is hopeful to provide a new path for the treatment of the rheumatoid arthritis.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs.
Background
Inflammation is a defensive response process of living tissue with vascular system to injury factors, which is closely related to various diseases. The research of inflammation and related phenomena (including the establishment of an inflammation model, the discovery of inflammatory response factors, the relation between the response factors and the action mechanism of medicines, the relation between the inflammation and other diseases and the like) has important guiding significance on medicine development, early diagnosis of cancers, the research of various physiological processes, cancer treatment and the like.
Rheumatoid arthritis is a relatively common inflammation, which is one of autoimmune diseases. The incidence of these diseases in the population is about 1%, at least 3000 tens of thousands of patients worldwide, affecting mainly women, increasing the risk of heart disease, lymphoma, diabetes, stroke and lung disease, possibly reducing the life expectancy of the patients by 10-15 years. At present, the pathogenesis of rheumatoid arthritis is not clear, but a plurality of breakthrough findings on novel cells, molecules, pathways and the like in the related fields are reported in the journal of international top academy successively, and the market scale of rheumatoid arthritis also shows a remarkable increase. Currently, drugs for rheumatoid arthritis are mainly classified into nonsteroidal anti-inflammatory drugs and antirheumatic drugs for improving the disease conditions, including targeted drugs, biological agents, and the like. Related agents such as targeted inhibition of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (il-6), and non-receptor tyrosine kinase (JAK) have shown potent clinical efficacy. However, these drugs generally have low response effect, are liable to cause toxic and side effects such as viral infection and malignant tumor, and are limited in use in clinical long-term administration. Therefore, the development of new rheumatoid arthritis therapeutic drugs has very important scientific and practical significance.
Nitrofurantoin has the English name of Nitrofurantoin and the chemical formula of C 8 H 6 N 4 O 5 The CAS number is 67-20-9, is an antibacterial drug with broad-spectrum antibacterial activity, can be clinically used for urinary system infection and the like caused by sensitive bacteria, and has clinically confirmed clinical effectiveness and safety. At present, nitrofurantoin has not been used for resisting rheumatoid arthritisReport of treatment of inflammation.
Disclosure of Invention
The invention provides application of nitrofurantoin in preparing medicines for treating rheumatoid arthritis. The nitrofurantoin originally used as an antibacterial drug is applied to the treatment of the rheumatoid arthritis, enriches the variety of the medicines for treating the rheumatoid arthritis, and is hopeful to provide a new path for the treatment of the rheumatoid arthritis.
The invention is realized by the following technical scheme:
the invention provides application of nitrofurantoin in preparing medicines for treating rheumatoid arthritis.
Based on the same inventive concept, the invention provides a medicine for treating rheumatoid arthritis, and the effective components of the medicine comprise nitrofurantoin.
Based on the same inventive concept, the invention provides application of nitrofurantoin in preparing a medicine for inhibiting synovial lining cell proliferation.
Based on the same inventive concept, the invention also provides application of nitrofurantoin in preparing a medicament for inhibiting osteoporosis.
Based on the same inventive concept, the invention also provides application of nitrofurantoin in preparing a medicament for inhibiting bone loss.
One or more technical solutions in the embodiments of the present invention at least have the following technical effects or advantages:
1. the application of the nitrofurantoin in preparing the anti-rheumatoid arthritis medicine, which applies the nitrofurantoin originally used as an antibacterial medicine to the treatment of the rheumatoid arthritis, enriches the variety of the rheumatoid arthritis treatment medicine and is expected to provide a new path for the treatment of the rheumatoid arthritis.
2. The application of the nitrofurantoin in preparing the anti-rheumatoid arthritis medicament can obviously improve the symptom of the rheumatoid arthritis of mice, obviously reduce proliferation of synovial lining cells, obviously inhibit osteoporosis and bone loss caused by the rheumatoid arthritis, obviously reduce expression of inflammatory factors (IL-1 beta, I L-6, IL-17, IL-23) and simultaneously promote expression of anti-inflammatory cytokines (I L-10), so that the nitrofurantoin can be used for treating the rheumatoid arthritis.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the therapeutic effect of nitrofurantoin on rheumatoid arthritis.
FIG. 2 shows the effect of nitrofurantoin on various inflammatory factors.
Detailed Description
The advantages and various effects of the present invention will be more clearly apparent from the following detailed description and examples. It will be understood by those skilled in the art that these specific embodiments and examples are intended to illustrate the invention, not to limit the invention.
Throughout the specification, unless specifically indicated otherwise, the terms used herein should be understood as meaning as commonly used in the art. Accordingly, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification will control.
Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or may be prepared by existing methods.
The whole idea of the invention is as follows:
at present, the therapeutic drugs for rheumatoid arthritis are relatively deficient, so that the development of new rheumatoid arthritis target drugs has very important scientific and practical significance.
Nitrofurantoin is an antibacterial drug with broad-spectrum antibacterial activity, can be clinically used for urinary system infection and the like caused by sensitive bacteria, and has clinically confirmed clinical effectiveness and safety. At present, the furantoin has not been reported for the treatment of rheumatoid arthritis.
The inventors found through a large number of experiments that nitrofurantoin can significantly improve the symptoms of rheumatoid arthritis of mice, including: obviously reduces proliferation of synovial lining cells, obviously inhibits osteoporosis and bone loss caused by rheumatoid arthritis, obviously reduces expression of inflammatory factors (IL-1 beta, I L-6, IL-17, IL-23), and promotes expression of anti-inflammatory cytokines (I L-10). Based on this, the present invention proposes to apply nitrofurantoin, which is originally an antibacterial drug, to the treatment of rheumatoid arthritis. Enriches the variety of medicines for treating rheumatoid arthritis and is expected to provide a new path for treating rheumatoid arthritis.
The application of nitrofurantoin in the preparation of anti-rheumatoid arthritis drugs will be described in detail with reference to examples and experimental data.
Example 1
This example describes an animal model trial of nitrofurantoin for the treatment of rheumatoid arthritis comprising the steps of:
(1) Animal information: animals were derived from Hunan Style Lekka laboratory animal Co., ltd, C57 mice, 20, females, 4-6 weeks old, and were bred in the absence of specific pathogens (specific pathogen free, SPF). The raising environment is at 22-26 ℃ and the relative humidity is 50-60%, and the artificial illumination is 12h each. And (5) carrying out adaptive feeding for 7 days.
(2) After the completion of the adaptive feeding, the mice were randomly divided into a blank group (n=5) and a rheumatoid arthritis model group (n=15). Wherein the blank control group: normal feeding is carried out without any operation; rheumatoid arthritis model group (n=15): the common modeling method of rheumatoid arthritis is adopted, namely, the II type collagen is fully and uniformly mixed with Freund's complete adjuvant to prepare 2mg/mL emulsion, and the emulsion is injected into the left foot pad and the right foot pad respectively according to the dosage of 50 uL/dose, and the immunity is enhanced after 1 week.
(3) Packet intervention. After the modeling is completed, the rheumatoid arthritis model group (n=15) is randomly divided into a model group (n=5), a nitrofurantoin group (n=5) and a baryta group (n=5); wherein the model set: and (3) normal feeding is performed without any operation. Nitrofurantoin group: the tail vein is injected with nitrofurantoin, the drug quantity is 2mg/kg, the drug concentration is 0.4mg/mL, the injection quantity is 0.1 mL/dose, once in 2 days, and the continuous intervention is carried out for 40 days. The barbitinib group is injected with the barbitinib by tail vein, the drug quantity is 2mg/kg, the drug concentration is 0.4mg/mL, the injection quantity is 0.1 mL/dose, once in 2 days, and the continuous intervention is carried out for 40 days. At the time of intervention, weighing and arthritis scoring tests were performed daily.
(4) And (5) obtaining materials. After the intervention, the mice were anesthetized with 1% sodium pentobarbital, and blood and hind limb paw were removed. If the animal is found to be dead, 100mg/kg sodium pentobarbital is used for anesthesia until no heart beat and no respiration are carried out, and the animal death is determined.
(5) Micro-CT test: instrument model: skyscan 1276Burker
Fixing and preserving the specimen: firstly, placing the prepared specimen into 4% paraformaldehyde solution for fixing for 24-48 hours; then, taking out the sample, and flushing the sample with phosphate buffer solution for three times; finally, the specimen is put into 75% alcohol solution for preservation for standby, and then sent for Micro-CT scanning.
(6) H & E staining:
I. when cutting tissue, a sharp knife or a shear is used, and when cutting tissue, the cut tissue is pulled back from the root of the knife. And (3) placing the plane to be cut of the fixed left paw tissues of the mice downwards at the bottom of a plastic embedding box, and performing dewatering and waxing embedding according to the conventional steps.
II, slicing: before slicing, the embedded tissue sample is frozen at the temperature of minus 20 ℃, and the tissue can be sliced after reaching proper hardness, wherein the slicing thickness is 3 mu m, and the patch is too thick and is not firm, so that the observation under a lens is not facilitated. Embedding makes the upper and lower parts of the tissue have certain edges, which is beneficial to continuous slicing and can avoid tissue shrinkage during the expansion.
III, spreading and baking: the water bath spreads out the slice, drags out the slice, and the slice is carefully attached to the glass slide, the hand is stable during the patch, and the hand needs to have a downward stretching action. And controlling the slice, putting the slice into a slice spreading device for spreading, paying attention to make the slice bubble-free, flatly sticking and tightly sticking, and timely baking the slice.
H & E staining: 1) Conventionally dewaxing tissue sections to water; 2) Slightly washing with water for 1-2min; 3) Hematoxylin semen staining for 3-6min; 4) Washing off hematoxylin semen with running water for 1-2min; 5) 1-3s of 1% hydrochloric acid alcohol; 6) Slightly washing with water for 1-2s; 7) Returning the blue promoting liquid for 5-10s; 8) Flushing with running water for 15-30s; 9) 0.5% eosin staining for 2-3min;10 Distilled water slightly washed for 1-2s;11 80% ethanol for 15-30s;12 95% ethanol for 15-30s;13 Absolute ethanol 1-2s;14 Xylene (I) 2-3s;15 2-3s for xylene (II); 16 A) neutral gum encapsulation.
V, image acquisition: the image system Leica Application Suite collects the relevant parts of the sample by taking pictures through a microscope.
(7) Serum inflammatory factor test:
a. dilution of standard: preparing 6 small test tubes, sequentially numbering, adding 110uL of standard substance diluent into each small test tube, then adding 110uL of original concentration standard substance into one test tube with the numbered number, and fully and uniformly mixing; then 110uL is taken from the test tube and added into a second test tube, and the mixture is fully and uniformly mixed; then 110uL is taken from the test tube and added into a third test tube, and the mixture is fully and uniformly mixed; then 110uL is taken from the test tube and added into a fourth test tube, and the mixture is fully and uniformly mixed; then 110uL is taken from the test tube and added into a fifth test tube, and the mixture is fully and uniformly mixed; 110uL was then removed from the tube and discarded. A sixth tube was used as standard No. 0.
b. Sample adding: a standard hole, a blank hole and a sample hole are formed in the enzyme-labeled coated plate, and 50uL of standard substances with different concentrations are sequentially added into the standard hole; the sample wells were filled with 40uL of sample followed by 10uL of biotin-labeled antibody.
c. Enzyme addition and incubation: in addition to the blank wells, 50uL of enzyme-labeled reagent was added to each well, and the wells were incubated in a 37℃incubator for 30 minutes after membrane sealing with a sealing plate.
d. Washing: diluting the concentrated washing liquid with distilled water 30 times, carefully removing the sealing plate film, discarding the liquid in the holes, spin-drying, filling each hole with the washing liquid, standing for 30 seconds, discarding, repeating for 5 times, and drying.
e. Color development: adding 50uL of a color developing agent A and 50uL of a color developing agent B into each hole, gently shaking and uniformly mixing, and developing for 10 minutes at 37 ℃ in a dark place.
f. Termination and measurement: adding 50uL of stop solution into each hole to stop the reaction; the absorbance (OD value) of each well was measured sequentially at a wavelength of 450nm in a blank Kong Diaoling, and the measurement was performed within 15 minutes after the addition of the stop solution.
The test results are shown in FIG. 1.
After the experiment is finished, three groups of data are randomly taken for statistical analysis, and the result is as follows: figure 1A shows a schematic of the establishment of a model of rheumatoid arthritis mice and drug intervention, scoring of rheumatoid arthritis in different groups and palm thickness. From the figure, the nitrofurantoin can obviously improve the symptoms of the rheumatoid arthritis, and the curative effect is equivalent to that of the commercial drug barekitinib. FIG. 1B shows the results of the sole Micro-CT image and related bone analysis parameters of mice of the no-use group. As can be seen from the figure, the rheumatoid arthritis group has typical characteristics of bone loss, and the number of trabeculae (Tb, N) and Bone Mineral Density (BMD) are reduced, indicating that the rheumatoid arthritis mice developed more severe osteoporosis and bone loss; the CT images, tb, N and BMD values of the drug intervention group (namely the nitrofurantoin group and the barbitinib group) are obviously improved or increased relative to those of the rheumatoid arthritis group, so that the nitrofurantoin has better curative effect. FIG. 1C shows H & E staining of joint sites in different groups of mice, from which it can be seen that the rheumatoid arthritis group (i.e., RA model group) produced significant synovial lining cell proliferation (Synovial lining cells hyperplasia); the proliferation of the drug intervention group is obviously inhibited. FIG. 2 shows typical concentrations of inflammatory factors or anti-inflammatory cytokines in serum from different groups of mice, showing that the drug group significantly reduced inflammatory factor expression (IL-1β, IL-6, IL-17, IL-23) and promoted anti-inflammatory cytokine expression (IL-10).
The above results all indicate that: nitrofurantoin can well relieve the symptoms of rheumatoid arthritis, inhibit the expression of various inflammatory factors and has good curative effect on the rheumatoid arthritis.
Finally, it is also noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (5)
1. The application of nitrofurantoin in preparing medicine for treating rheumatoid arthritis is provided.
2. A medicament for treating rheumatoid arthritis, wherein the active ingredient of the medicament comprises nitrofurantoin.
3. Use of nitrofurantoin in the manufacture of a medicament for inhibiting synovial lining cell proliferation.
4. The application of nitrofurantoin in preparing medicine for inhibiting osteoporosis is provided.
5. The application of nitrofurantoin in preparing medicine for inhibiting bone loss is provided.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311506331.8A CN117643588A (en) | 2023-11-13 | 2023-11-13 | Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311506331.8A CN117643588A (en) | 2023-11-13 | 2023-11-13 | Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117643588A true CN117643588A (en) | 2024-03-05 |
Family
ID=90045787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311506331.8A Pending CN117643588A (en) | 2023-11-13 | 2023-11-13 | Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117643588A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070202077A1 (en) * | 2005-12-02 | 2007-08-30 | Brodsky Robert A | Use of High-Dose Oxazaphosphorine Drugs for Treating Immune Disorders |
| US20090022706A1 (en) * | 2007-07-20 | 2009-01-22 | Auspex Pharmaceuticals, Inc. | Substituted cyclohexenes |
| CN109420161A (en) * | 2017-08-25 | 2019-03-05 | 石家庄石强生物科技有限公司 | Composition containing SOD |
| US20190367492A1 (en) * | 2014-12-31 | 2019-12-05 | Auspex Pharmaceuticals, Inc. | Cyclopropane Carboxamide Modulators of Cystic Fibrosis Transmembrane Conductance Regulator |
| WO2021096972A1 (en) * | 2019-11-11 | 2021-05-20 | The Regents Of The University Of California | Polymeric nanoparticles that target liver sinusoidal endothelial cells to induce antigen-specific immune tolerance |
-
2023
- 2023-11-13 CN CN202311506331.8A patent/CN117643588A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070202077A1 (en) * | 2005-12-02 | 2007-08-30 | Brodsky Robert A | Use of High-Dose Oxazaphosphorine Drugs for Treating Immune Disorders |
| US20090022706A1 (en) * | 2007-07-20 | 2009-01-22 | Auspex Pharmaceuticals, Inc. | Substituted cyclohexenes |
| US20190367492A1 (en) * | 2014-12-31 | 2019-12-05 | Auspex Pharmaceuticals, Inc. | Cyclopropane Carboxamide Modulators of Cystic Fibrosis Transmembrane Conductance Regulator |
| CN109420161A (en) * | 2017-08-25 | 2019-03-05 | 石家庄石强生物科技有限公司 | Composition containing SOD |
| WO2021096972A1 (en) * | 2019-11-11 | 2021-05-20 | The Regents Of The University Of California | Polymeric nanoparticles that target liver sinusoidal endothelial cells to induce antigen-specific immune tolerance |
| US20220395563A1 (en) * | 2019-11-11 | 2022-12-15 | The Regents Of The University Of California | Polymeric nanoparticles that target liver sinusoidal endothelial cells to induce antigen-specific immune tolerance |
Non-Patent Citations (3)
| Title |
|---|
| HILE`NE LIN等: "Protective role of systemic furin in immune response–induced arthritis", ARTHRITIS & RHEUMATISM, vol. 64, no. 9, 27 August 2012 (2012-08-27), pages 2878, XP055068020, DOI: 10.1002/art.34523 * |
| JEREZ, MA. JOSE等: "Combined use of pharmacophoric models together with drug metabolism and genotoxicity "in silico" studies in the hit finding process", JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, vol. 27, no. 1, 8 January 2013 (2013-01-08), pages 79 - 90 * |
| 陈梦琳: "急性细菌性关节炎的病原菌特征及药敏实验分析", 广州医科大学学报, vol. 49, no. 2, 15 April 2021 (2021-04-15), pages 49 - 53 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Roark et al. | Physiological and histological phenomena of the bovine estrual cycle with special reference to vaginal-cervical secretions | |
| CN113768945B (en) | Application of geniposide in preparation of medicine for treating oligospermia | |
| CN112494505B (en) | Application of echinacoside in preparation of medicine for treating neuropathic pain | |
| CN113577047A (en) | Application of preparation for regulating and controlling expression level of ApoC3 in preparation of medicine for preventing or treating insulin-resistant polycystic ovarian syndrome | |
| KR102182563B1 (en) | Use of tungsten (vi) salts for the treatment of female infertility in non-diabetic mammals | |
| CN117643588A (en) | Application of nitrofurantoin in preparation of anti-rheumatoid arthritis drugs | |
| CN114225011B (en) | Composite preparation for preventing and treating GSM and application thereof | |
| Samour | The reproductive biology of the budgerigar (Melopsittacus undulatus): semen preservation techniques and artificial insemination procedures | |
| CN107540643A (en) | Ganoderma lucidum composition GL 1 and as estrogen replacement in terms of application | |
| US9186421B2 (en) | Establishment of rhesus monkey model of autoimmunity type 1 diabetes | |
| CN101095743A (en) | Exterior-applied medicine composition for treating gynecologic diseases and method of making the same and the use thereof | |
| CN105126118B (en) | Application of the long non-coding ribonucleic acid uc.48+ siRNAs in preparing diabetes and complication drug | |
| CN103656091A (en) | Water-soluble matrix traditional Chinese medicine ointment preparation for treating diabetic foot, and preparation method and application thereof | |
| CN105311300A (en) | Pharmaceutical composition, herba houttuyniae suppository and preparation method and application | |
| CN111481535A (en) | Application of IDHP in preparation of anti-septicemia and myocardial damage drug induced by IDHP | |
| CN110367190A (en) | A kind of method of Liver Damage in Rats model foundation | |
| CN112402428A (en) | Application of remazolam in treatment of postoperative hyperalgesia induced by opioid | |
| DeMatteo et al. | Semen collection and artificial insemination in the common piping guan (Pipile cumanensis cumanensis): potential applications for Cracidae (Aves: Galliformes) | |
| Klaphake et al. | Effects of leuprolide acetate on selected blood and fecal sex hormones in Hispaniolan Amazon parrots (Amazona ventralis) | |
| CN109913541A (en) | The application of GPR1 target spot and its antagonist in infertile related disease | |
| Allegretti et al. | Experimental allergic encephalomyelitis in irradiated rats | |
| CN109700791B (en) | Application of neosinomenine in preparing medicine for treating benign prostatic hyperplasia | |
| Sutrisno et al. | Genistein Affects Estrogen Receptor Alpha (ER-α)/Estrogen Receptor Beta (ER-β) Ratio, and Nuclear Factor-Kappa Beta (NF-κβ) in Mice Model of Endometriosis. | |
| CN109745314A (en) | Application of the iron chelating agent Deferasirox (DFX) in the drug for the treatment of cervical carcinoma | |
| CN113476440A (en) | Application of sesamin in preparation of medicine for treating spermatogenic dysfunction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |